Hexane → [5-(Tert-butylsulfamoyl)pyridin-3-yl]boronic acid

Temperature

-78 °C

A solution of 5-bromo-pyridine-3-sulfonic acid tert-butylamide (CAS 911111-80-3; WO2010007) (11.4 g, 39 mmol) in tetrahydrofuran (200 ml) was treated with triisopropyl borate (33 ml, 144 mmol) and cooled to −78° C. A solution of n-butyl lithium in hexane (1.6M, 90 ml, 144 mmol) was added cautiously whereby the reaction temperature was kept below −60° C. The reaction mixture was stirred for 3.5 hours at −78° C. For the workup, the reaction mixture was treated with water (300 ml), stirred at room temperature for 15 minutes, and then extracted with ethyl acetate. The aqueous layer was separated and acidified with hydrochloric acid (3M) to pH 4. Thereafter, solid sodium chloride was added, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulphate, filtered, and the solvent evaporated to give a light yellow amorphous product. For purification, the residue was dissolved at room temperature in a 3:1-mixture of water and isopropanol (100 ml). More water was added (total volume: 200 ml), then the solution cooled to 0° C., stirred for 30 minutes. The precipitate was filtrated, the solid washed with water and dried at high vacuum to give the 5-(N-tert-butylsulfamoyl)pyridin-3-ylboronic acid (5.06 g, 50% yield) as an off-white solid. MS (ISN): m/z=257.1 [M−H]−.

1. customwas kept below −60° C
2. stirringstirred at room temperature for 15 minutes
3. extractionextracted with ethyl acetate
4. customThe aqueous layer was separated
5. additionThereafter, solid sodium chloride was added
6. extractionthe aqueous layer was extracted with ethyl acetate
7. dry with materialdried over magnesium sulphate
8. filtrationfiltered
9. customthe solvent evaporated
10. customto give a light yellow amorphous product
11. customFor purification
12. dissolutionthe residue was dissolved at room temperature in a 3
13. additionMore water was added (total volume: 200 ml)
14. temperaturethe solution cooled to 0° C.
15. stirringstirred for 30 minutes
16. filtrationThe precipitate was filtrated
17. washthe solid washed with water
18. customdried at high vacuum

ORD record

ord-7d626e0c206c45dfa978605bf2a0498e

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08877744B2